Review
Experimental obstructive cholestasis: the wound-like inflammatory liver response
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* Corresponding author: Jaime Arias jariasp@med.ucm.es
1 Department of Surgery I, School of Medicine, Complutense University of Madrid, Spain
2 Neurosciences Laboratory, School of Psychology, University of Oviedo, Asturias, Spain
3 Plastic and Reconstructive Surgery Unit, Getafe Hospital, Madrid, Spain
4 General Surgery Unit, Monte Naranco Hospital, Oviedo, Consejería de Salud y Servicios Sanitarios, Principado de Asturias, Spain
5 Health Sciences School, King Juan Carlos University, Madrid, Spain
Fibrogenesis & Tissue Repair 2008, 1:6 doi:10.1186/1755-1536-1-6
Published: 3 November 2008Abstract
Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them.
Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis.
It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.